[MS11] Dynamics of Pattern Formation and Morphogenesis in Biological Systems

[MS11-03] Emergence of digit-like structures through mechanical instabilities: A hybrid computational and experimental study

*Antoine Diez^1,2, Rio Tsutsumi², Steffen Plunder² (1. RIKEN iTHEMS (Japan), 2. ASHBi, Kyoto University (Japan))

Keywords:

Limb morphogenesis,Agent-Based model,PDE

Digit formation has traditionally been explained through Turing models incorporating Sox9-Bmp-Wnt network interactions, successfully predicting digit initiation sites. On a tissue-level, cell movement is known to transition from solid-to-fluid-like cell movements. However, these existing models both fail to explain the cellular mechanism of mesenchymal cells to interpret molecular signals and translate them into the mechanical forces that drive digit formation. Key challenges here are the inherent limitations of in vivo observation and the complex nature of three-dimensional, unorganized mesenchymal morphogenesis, which differs significantly from better-understood epithelial or two-dimensional morphogenic processes. Using a novel limb-like organoid culture system, we obtained detailed in vitro data that provides deeper insights into emergence of digit-like structures. Through agent-based modeling, we demonstrate how symmetric mechanical laws combined with a simple signaling model could generate symmetry breaking and digit formation. These results combined with ongoing mathematical analysis then suggest that digit formation at the organoid level can emerge from mechanical fingering instabilities. Our findings point to mechanical cues potentially playing a complementary role alongside traditional Turing patterns in driving digit morphogenesis.